Mutations in the Drosophila EGF receptor gene affect a range of vital and developmental processes. The long-term goal of this research program is to define the role(s) of growth factor receptor tyrosine kinases in development through detailed genetic and molecular genetic studies in this model system. It is hoped that the results of these studies can be extended to vertebrate systems and thus shed light on the roles of cellular and transforming growth factor receptor tyrosine kinases in normal development and in neoplastic disease. The Specific Aims of the current proposal are: (1). To complete the genetic characterization of extragenic mutations that suppress the Ellipse (Elp) class of EGF receptor mutations. Elp alleles manifest a dominant rough eye phenotype. Five suppressor gene mutations induced by P element mutagenesis have been isolated and will be analyzed with respect to interaction with recessive EGF receptor gene mutations and with each other. (2). To analyze a subset of the Elp suppressors at the molecular level. On the basis of the genetic tests, certain of the Elp suppressor mutations will be molecularly cloned and sequenced to learn the structure/identity of elements of the EGF receptor signaling pathway. (3). To identify genes acting as extragenic suppressors of recessive DER gene mutations in tissues other than the eye. Mutations of this class would represent gain-of-function mutations in elements of the DER signaling pathway that may not function in the eye. These results will reveal whether the same, different, or partially overlapping set of elements functions in the EGF receptor signaling pathway in different tissues. (4). To isolate new alleles of the Elp class in a defined genetic background to define the mechanism or mechanisms that can activate the dominant mutant phenotype in EGF receptor. Genetic tests will be carried out to assess the potential for variability in the Elp phenotype. Companion studies at the molecular level will define the structural changes in the protein accompanying phenotypic variation.